The Tissue Core will play an important role in this Program Project by providing detailed histopathological characterization of the tissue samples and by making available to the Research Projects a state-of-the-art biosafety level 3 (BSL3) suite, approved to work with BSE infectious material. The activities of the Tissue Core are carried out through three Specific Aims. In Specific Aim 1. the Core will determine presence, type, severity and anatomic distribution of the structural lesions as well as topography and pattern of scrapie PrP (PrPSc) in tissues from inoculated transgenic mice and actual animal host. Brain and, when needed, other tissues will be processed for histological and immunohistochemical examinations. Profiles of the histological lesions and maps of scrapie prion protein distribution will be made. They will be constructed to allow for the establishment of the histopathological phenotype. The centralized histological studies of all samples generated in this Program Project assures that tissue is processed and analyzed in the same way and will serve to homogenize results across the different locations in this project and make them directly comparable. Specific Aim 2 deals with making the BSL3 laboratories available for analyses of BSE infected tissues and other experiments requiring BSL3 conditions. The Core B possess a state-of-the-art 1500 sq. ft. BSL3 suite that is fully equipped and certified to work with any kind of PrPSc including BSE. The BSL3 suite will be available, with technical support, to members who are certified to carry out the studies proposed in the Program Project. In Specific Aim 3. the Tissue Core will accession and store the tissues acquired from the other members of the programs, abiding by the stringent storage conditions of BSE infected tissue. The tissue samples will be fully accessible to the certified members for experimentation to be conducted in the BSL3 suite. The BSL3 suite has personnel trained to maintain and manage the facility including storage of highly sensitive tissues, which requires dedicated freezers and daily inspections certifying the presence of the stored material. Through these three Specific Aims, the Core B provides services that are essential for the success of this Program Project.